Modeling microRNA-driven post-transcriptional regulation using exon–intron split analysis in pigs

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The contribution of microRNAs (miRNAs) to mRNA post-transcriptional regulation has often been explored by the post hoc selection of downregulated genes and determining whether they harbor binding sites for miRNAs of interest. This approach, however, does not discriminate whether these mRNAs are also downregulated at the transcriptional level. Here, we have characterized the transcriptional and post-transcriptional changes in mRNA expression in two porcine tissues: gluteus medius muscle of fasted and fed Duroc gilts and adipose tissue of lean and obese Duroc–Göttingen minipigs. Exon–intron split analysis of RNA-seq data allowed us to identify downregulated mRNAs with high post-transcriptional signals in fed or obese states, and we assessed whether they harbor binding sites for upregulated miRNAs in any of these two physiological states. We found 26 downregulated mRNAs with high post-transcriptional signals in the muscle of fed gilts and 21 of these were predicted targets of miRNAs upregulated in fed pigs. For adipose tissue, 44 downregulated mRNAs in obese minipigs displayed high post-transcriptional signals, and 25 of these were predicted targets of miRNAs upregulated in the obese state. These results suggest that the contribution of miRNAs to mRNA repression is more prominent in the skeletal muscle system. Finally, we identified several genes that may play relevant roles in the energy homeostasis of the pig skeletal muscle (DKK2 and PDK4) and adipose (SESN3 and ESRRG) tissues. By differentiating transcriptional from post-transcriptional changes in mRNA expression, exon–intron split analysis provides a valuable view of the regulation of gene expression, complementary to canonical differential expression analyses.

OriginalsprogEngelsk
TidsskriftAnimal Genetics
Vol/bind53
Udgave nummer5
Sider (fra-til)613-626
ISSN0268-9146
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The present research work was funded by grants AGL2013‐48742‐C2‐1‐R and AGL2013‐48742‐C2‐2‐R awarded by the Spanish Ministry of Economy and Competitivity. E. Mármol‐Sánchez was funded with a PhD fellowship FPU15/01733 awarded by the Spanish Ministry of Education and Culture. YRC is the recipient of a Ramon y Cajal fellowship (RYC2019‐027244‐I) from the Spanish Ministry of Science and Innovation.

Funding Information:
The authors would like to thank the Department of Veterinary Animal Sciences in the Faculty of Health and Medical Sciences of the University of Copenhagen for providing sequencing data and their facilities and resources for qPCR experiments. We also acknowledge Selección Batallé S.A. for providing animal material and the support of the Spanish Ministry of Economy and Competitivity for the Center of Excellence Severo Ochoa 2020–2023 (CEX2019‐000902‐S) grant awarded to the Centre for Research in Agricultural Genomics (CRAG, Bellaterra, Spain). Thanks also to the CERCA Programme of the Generalitat de Catalunya for their support.

Publisher Copyright:
© 2022 Stichting International Foundation for Animal Genetics.

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